Prefilled hypodermic syringes containing medicaments purporting to be sterile are an important means of delivering safe single dose medicaments to the point of administration. The volume of products prepared in this manner is continuallly increasing due to the advantages of this delivery system.
However, in view of the structural complexities of this type of syringe, there are many problems involved in the fabrication of a prefilled syringe container which assures the sterility of the contents, is economically practicable, and is convenient to use. In particular, the sterility problems associated with these prefilled hypodermic syringes have been recognized by both governmental agencies (e.g. FDA) and industrial associations (e.g. Parenteral Drug Association), and various guidelines and procedures have been provided for assuring the sterility of these products. These procedures are costly and difficult to carry out. The sterility problems come from three (3) sources, (i) initial sterilization, (ii) aseptic filling and sealing and (iii) maintenance of sterility during the normal shelf life of the product.
It is difficult, due to the nature of the hypodermic syringe now in use, to design one which can be effectively sterilized prior to aseptically filling with the required sterile medicament. The aseptic filling and sealing operation is also more difficult to accomplish with a hypodermic syringe container rather than the standard serum vial or ampule which is currently employed for packaging injectible pharmaceuticals purporting to be sterile. The added complex procedures necessary to prefill a hypodermic syringe result in a greater possibility of contamination and the consequent presence of nonsterile units in the filling lot.
Another problem with the currently available prefilled hypodermic syringes is the limited or questionable sterility integrity of the container during the expected shelf life of the product. This limitation is due primarily to the typical design of the closure and sealing systems employed.
Many approaches have been tried to meet this problem of sterility. In the hypodermic syringes disclosed in U.S. Pat. Nos. 4,314,556; 4,317,446; 4,281,653 and 4,235,235, the elastomeric closure which also serves as the piston or plunger is placed entirely inside the prefilled syringe barrel or cylinder. The assurance of continuing sterility therefore is limited only to the pressure of the one or more annular rings on the rim of the elastomeric piston or plunger. Since the elastomeric piston or plunger must ultimately be depressed in the syringe cylinder in order to express the injection dose, the fit of the piston cannot of necessity be extremely tight, since if it were, it would hinder the movement of the piston or plunger.
Sometimes lubricants have been employed to ease the movement of the plunger. Usually, the plunger and the syringe barrel are coated with a medical grade silicone. However, the amount of the lubricant being used must be carefully controlled since at times these lubricants may end up as globules in the liquid medicament and this can be very dangerous to the patient receiving the injection.
Another limitation in the design of some of the currently marketed prefilled syringes is the needle assembly. In these units where the needle assembly is permanently affixed to the syringe barrel, a special shield and closure for the needle is necessary in order to prevent the contained medicament liquid from leaking out of the syringe barrel through the needle. In order to accomplish this the point of the needle is actually imbedded into an elastomeric shield. This sealing procedure must obviously be completed prior to the aseptic filling of the barrel with the sterile medicament. The sterilization of the empty syringe including the imbedded needle is usually accomplished by employment of steam or ethylene oxide gas. The limitations of this sterilization procedure are due to the nature of the seal employed with the needle assembly. The imbedding of the needle tip into the elastomeric shield results in a section of the needle being insulated from the sterilization process. This defect is shown in U.S. Pat. No. 4,317,446 and in many widely distributed prefilled hypodermic syringes now on the market.